As a lefty, I can echo many of the suggestions above. Rather than specific recommendations, though, let me break it down a bit.
If the knife has a carry clip, it should be reversible so the knife can be carried on the left side. Many Spyderco's fit this bill, but beware of the higher priced models, some do not.
The lock should be something that can be operated equally well from either hand. The best options on this are the Benchmade Axis lock, and the good old lock back. When buying Spyderco's beware that some of them are not lockbacks. The liner lock is not ambidextrous, but it can easily be operated left handed. One of my favorite knives right now is the Buck-Strider Tarani. It's aliner lock, but the clip reverses, and it is one smooth knife.
For one handed opening knives, holes are obviously ambi-dextrous, but some knives with studs have them on only one side, so beware. Buck Strider's used to be this way. The stud was reversible, but still a PITA.
Don't be afraid of good old lockbacks like the buck 110 and 112. They are extremely capable knives, and totally ambi. I usually have some small lockback in my pocket for the situations needing a non-frightening knive.
If anything, shopping for fixed blades is worse than for lockbacks. Very vew sheaths are amibdextrous, and carrying a knife on the 'wrong' side is downright dangerous, at times. Let me say that "Lifter4Him" has made me some great sheaths, so I can actually use my fixed blades.
Usually, right now, my pocket has a Benchmade mini-griptilian with partial serrations, and a Spyderco Native III. I love my Calypso Junior too, and have been carrying, as I said, the Tarani. There are other benchmades and spyderco's on my dresser, as well as a line of customized buck 110's. Life is good.
Hope this helps, a little. And remember, only lefties are in their right minds.
Cheers,
Al